A thermosensitive chitosan-based hydrogel for controlled release of insulin

Abstract

Present study aims at synthesizing a thermosensitive hydrogel for controlled release of insulin. According to a modified method, hydroxybutyl chitosan (HBC) hydrogel possessed thermal sensitivity is prepared which can form hydrogel at over 25°C. The HBC hydrogel is non-cytotoxic to mice fibroblasts cells (L929). Insulin is 100% entrapped in the hydrogel, 38% of which is released in vitro from the concentration of 5% hydrogel after 48 h, whereas by enzymolysis with lysozyme, 80% of the total insulin is released after 48 h. This study suggests that HBC hydrogel could be utilized for controlled release of insulin in a non-invasive manner.

Keywords

hydroxybutyl chitosan / hydrogel / thermosensitive / insulin / controlled release

References

[1] Peng Q, Sun X, Gong T, . Injectable and biodegradable thermosensitive hydrogels loaded with PHBHHx nanoparticles for the sustained and controlled release <?Pub Caret?>of insulin. Acta Biomaterialia, 2013, 9(2): 5063-5069

[2] Westphal S A, Palumbo P J. A case for introducing insulin early in the treatment of type 2 diabetes mellitus. Insulin, 2006, 1(2): 65-69

[3] Yu S, Zhao Y, Wu F, . Nasal insulin delivery in the chitosan solution: in vitro and in vivo studies. International Journal of Pharmaceutics, 2004, 281(1-2): 11-23

[4] Chono S, Fukuchi R, Seki T, . Aerosolized liposomes with dipalmitoyl phosphatidylcholine enhance pulmonary insulin delivery. Journal of Controlled Release, 2009, 137(2): 104-109

[5] Portero A, Teijeiro-Osorio D, Alonso M J, . Development of chitosan sponges for buccal administration of insulin. Carbohydrate Polymers, 2007, 68(4): 617-625

[6] Lee Y C, Simamora P, Pinsuwan S, . Review on the systemic delivery of insulin via the ocular route. International Journal of Pharmaceutics, 2002, 233(1-2): 1-18

[7] Barichello J M, Morishita M, Takayama K, . Enhanced rectal absorption of insulin-loaded Pluronic F-127 gels containing unsaturated fatty acids. International Journal of Pharmaceutics, 1999, 183(2): 125-132

[8] Khafagy S, Morishita M, Onuki Y, . Current challenges in non-invasive insulin delivery systems: a comparative review. Advanced Drug Delivery Reviews, 2007, 59(15): 1521-1546

[9] Bhattarai N, Gunn J, Zhang M. Chitosan-based hydrogels for controlled, localized drug delivery. Advanced Drug Delivery Reviews, 2010, 62(1): 83-99

[10] Kim S, Nishimoto S K, Bumgardner J D, . A chitosan/β-glycerophosphate thermo-sensitive gel for the delivery of ellagic acid for the treatment of brain cancer. Biomaterials, 2010, 31(14): 4157-4166

[11] Lü S, Liu M, Ni B. An injectable oxidized carboxymethyl cellulose/N-succinyl-chitosan hydrogel system for protein delivery. Chemical Engineering Journal, 2010, 160(2): 779-787

[12] Chen C, Dong A, Yang J, . Preparation and properties of an injectable thermo-sensitive double crosslinking hydrogel based on thiolated chitosan/β-glycerophosphate. Journal of Materials Science, 2012, 47(5): 2509-2517

[13] Gong C, Shi S, Wu L, . Biodegradable in situ gel-forming controlled drug delivery system based on thermosensitive PCL–PEG–PCL hydrogel. Part 2: sol–gel–sol transition and drug delivery behavior. Acta Biomaterialia, 2009, 5(9): 3358-3370

[14] Ruel-Gariépy E, Shive M, Bichara A, . A thermosensitive chitosan-based hydrogel for the local delivery of paclitaxel. European Journal of Pharmaceutics and Biopharmaceutics, 2004, 57(1): 53-63

[15] Teles H, Vermonden T, Eggink G, . Hydrogels of collagen-inspired telechelic triblock copolymers for the sustained release of proteins. Journal of Controlled Release, 2010, 147(2): 298-303

[16] Park D, Wu W, Wang Y. A functionalizable reverse thermal gel based on a polyurethane/PEG block copolymer. Biomaterials, 2011, 32(3): 777-786

[17] Huynh D P, Nguyen M K, Pi B S, . Functionalized injectable hydrogels for controlled insulin delivery. Biomaterials, 2008, 29(16): 2527-2534

[18] Wei C Z, Hou C L, Gu Q S, . A thermosensitive chitosan-based hydrogel barrier for post-operative adhesions’ prevention. Biomaterials, 2009, 30(29): 5534-5540

[19] Wang Q Q, Kong M, An Y, . Hydroxybutyl chitosan thermo-sensitive hydrogel: a potential drug delivery system. Journal of Materials Science, 2013, 48(16): 5614-5623

[20] Dang J M, Sun D D N, Shin-Ya Y, . Temperature-responsive hydroxybutyl chitosan for the culture of mesenchymal stem cells and intervertebral disk cells. Biomaterials, 2006, 27(3): 406-418

[21] Peng Y, Han B, Liu W, . Preparation and antimicrobial activity of hydroxypropyl chitosan. Carbohydrate Research, 2005, 340(11): 1846-1851

Acknowledgements

This work was supported by a grant from International S&T Cooperation Program of China (Grant No. 2013DFG32880), the National Natural Science Foundation of China (Grant No. 31000423), and the Doctoral Fund of Ministry of Education of China (Grant No. 20120132110012)

RIGHTS & PERMISSIONS

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg